Abstract: This study investigated the effect of γ-oryzanol extracted from Rice Bran Oil (RBO) on rats fed a high-cholesterol diet. γ-oryzanol content in RBO were determined and separated by HPLC. γ-oryzanol was administered at different doses (250, 500 and 750 mg/100 g diet) for 50 days. It was found that serum Total Cholesterol (TC) concentration significantly decreased compared with the control. In addition, serum High Density Lipoprotein Cholesterol (HDL-C) levels, total protein and albumin were significantly increased and the concentration of Triglyceride (TG), Total Lipids (TL), Low-Density Lipoprotein Cholesterol (LDL-C), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), urea and creatinine were significantly decreased after 50 days of the administration. Also, risk ratio and A/G ratio were calculated. The obtained results indicated that using 500 mg and 750 mg from γ-oryzanol were more beneficial than using 250 mg for lowering cholesterol in hyper-cholesterolemic rats. It could be recommended to use γ-oryzanol as natural source for cholesterol-lowering and effectiveness of doses used is due to 750 mg/100 g.Keywords: Rice bran oil; γ-oryzanol; Feed efficiency; Total cholesterol; High density lipoprotein; Low density lipoprotein; Risk ratio; Total lipids; Triglycerides; Total protein; HPLC